Protein targeting and translocation at the endoplasmic reticulum membrane--through the eye of a needle?

Abstract

SRP-dependent and SRP-independent targeting routes deliver precursor proteins to the ER membrane translocon. These precursors are translocated into (for membrane proteins) and across (for secretory protein) the ER membrane via aqueous channels composed of oligomers of the Sec61 complex. Both ends of the ER translocon are 'gated' and the opening and closing of these gates are closely regulated. The lateral exit of hydrophobic polypeptide regions into the phospholipid bilayer also appears to be a carefully controlled process. Accessory components are transiently associated with active ER translocation sites and modify the nascent polypeptide as it appears on the luminal side of the membrane.